Figure 6.

Potential role of the hypoxia inducible factor‐1α (HIF‐1α)–interleukin (IL)−33 axis in regulating intestinal mucosal inflammation in inflammatory bowel disease (IBD). Under inflammatory conditions, the intestinal mucosa encounters different micro‐environmental challenges, including increased expression of proinflammatory cytokines and low oxygen tension. An increase of tumour necrosis factor (TNF) could up‐regulate HIF‐1α expression through activating nuclear factor (NF)‐кB in a hypoxia‐independent manner, which further promotes the expression of IL‐33 in in intestinal epithelial cell (IECs) by binding hypoxic response elements (HRE) in the promoter region of IL‐33. Importantly, IL‐33 facilitates mucosal inflammation via enhancing T helper type 2 (Th2)‐associated immune response and neutrophil recruitment, and prevents inflammatory responses by inducing the differentiation of regulatory immune cells such as regulatory T cell (T_reg) and alternatively activated (M2) macrophage. Additionally, IL‐33 may also activate fibroblast to accelerate wound healing. [Colour figure can be viewed at wileyonlinelibrary.com]